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Drake, the eldest child of two American expatriates, was born in Paris, France. Although her grandfather, Tracy Drake, had built the Drake Hotel in Chicago, Illinois, the Drakes lost their money in the 1929 stock-market crash when Drake was six years old. As a result, she was forced to return to the U.S. on the SS Île de France with her parents, brothers and a nanny. She grew up in Chicago; Westport, Connecticut; Washington, D.C.; Virginia, North Carolina; and New York City.

She went to twelve different schools, both private and public, before concentrating on theatre and acting at a junior college in Rock Creek Park, Maryland, near Washington, D.C.

After coming to the attention of the producer Hal Wallis, Drake was pressured by her agent to sign a Hollywood contract. She hated Hollywood and managed to get herself released from the contract by declaring herself insane. She returned to New York City and, in 1947, read for the director Elia Kazan for the lead role in the London company of the play Deep are the Roots. Later that year, Drake was selected by Kazan as one of the founding members of the Actors Studio.[1]

Drake subsequently gave up acting in order to focus on her other interests, such as writing. Using the name Betsy Drake Grant, her novel Children, You Are Very Little (1971) was published by Atheneum Books.

In July 1956, Drake survived the sinking of the Italian ocean liner SS Andrea Doria. At the time, she had been visiting Grant in Spain and was returning to the United States. She boarded the Doria along with dozens of other wealthy travelers and tourists at Gibraltar, which was one of many stops the ship made between her home port of Genoa and her final destination of New York. She sailed as a First Class passenger, occupying a single cabin on the ship's Boat Deck. When the Doria collided with the Stockholm, Drake waited with the other passengers for rescue, as the ship's severe list rendered half the Doria's lifeboats useless. She was among more than 700 people rescued from the Doria by the famed French passenger liner Ile de France.

Grant and Drake separated in 1958, remaining friends, and divorced in 1962. Their marriage constituted his longest union. Grant credited her with broadening his interests beyond his career, and with introducing him to the then-legal LSD therapy, which he claimed helped him finally to achieve a degree of mental peace. Later, Drake took LSD as a way of recovering from the trauma of divorce.